Effects of intravenous immunoglobulins on T-cell mediated, concanavalin A-induced hepatitis in mice.
Concanavalin A (ConA) activates T lymphocytes and causes T-cell mediated hepatic injury in mice. The intravenous administration of human immunoglobulins has beneficial effects in T-cell mediated diseases such as experimental autoimmune encephalomyelitis and adjuvant arthritis. In the present study, we examined the effects of intravenous immunoglobulins in a mouse model of T-cell mediated, acute liver injury induced by concanavalin A. Balb/c mice were inoculated with 12 mg/kg concanavalin A with or without intravenous immunoglobulins at doses of 0.4, 0.6, 0.8 g/kg body wt. The serum levels of liver enzymes, tumor necrosis factor-alpha, interferon-gamma and interleukin-6 were assayed 2, 6 and 24 h after concanavalin A administration. Intravenous immunoglobulins did not prevent concanavalin A-induced hepatitis, as manifested by elevation of serum aminotransferases and histopathological evaluation. The serum levels of tumor necrosis factor-alpha in mice pretreated with immunoglobulins, measured 2 h after ConA treatment were reduced, while interferon-gamma levels measured 6 h after ConA inoculation were 5-fold higher than control levels. There was no effect of intravenous immunoglobulins on the release of interleukin 6. In conclusion, these results indicate that intravenous immunoglobulin is not effective in preventing T-cell mediated concanavalin A-induced hepatitis. The increased secretion of interferon-gamma and the incomplete suppression of tumor necrosis factor-alpha release may explain the lack of efficacy of intravenous immunoglobulin in this experimental model.
Shirin
H
H
Department of Gastroenterology, E. Wolfson Medical Center, Holon, Israel.
Bruck
R
R
Aeed
H
H
Hershkoviz
R
R
Lider
O
O
Kenet
G
G
Avni
Y
Y
Halpern
Z
Z
D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D003208:Concanavalin A / Q000633:toxicity*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000494:pharmacology*; D007371:Interferon-gamma / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D013601:T-Lymphocytes / Q000276:immunology*; D000637:Transaminases / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016756:Immunoglobulins, Intravenous; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D003208:Concanavalin A; D007371:Interferon-gamma; D000637:Transaminases